OBJECTIVES: 1) To purify analytical amounts of the folate binding protein from leukemia cells and to analyze its chemical composition and physical properties. 2) To study the interaction of the folate binding protein with key intracellular folate coenzymes including its effect on biochemical reactions. 3) To correlate by radioimmunoassay the concentration of the folate binding protein in various tissues with the concentration of dihydrofolate reductase, thymidylate synthetase and intracellular folate. 4) To measure by radioimmunoassay FBP in serum of cancer patients and correlate the concentration with type and stage of the disease, and with therapy. 5) To study the factors that regulate the synthesis of the folate binding protein. 6) To measure the accumulation of methotrexate in free and bound intracellular compartments and the factors that regulate this distribution. 7) To develop a radioimmunoassay for dihydrofolate reductase and correlate concentration of immunoreactive protein with enzyme activity. 8) To purify analytical amounts of folate binder from milk, and determine whether it can sequester folate in vitro and in vivo. 9) To study the mechanism of guinea pig resistance to the toxic effects of methotrexate.